Role of Kv Channels in Neuroregeneration and Protection
Injury to the human central nervous system (CNS) is usually difficult to treat because of the limited regeneration capabilities of the neurons. Evidence suggests that the lack of CNS regeneration is due to the presence of inhibitory factors in the CNS environment. While there is clearly a great need for development of compounds that prevent neuronal degeneration or that promote the growth of neurons, clinical trials of neuroprotective compounds for use in a variety of neurodegenerative diseases have been largely unsuccessful. This invention relates to the identification of a family of ion channels are expressed when neurons are damaged. Additionally, function of these channels is required for apoptosis of damaged neurons. Accordingly, blockers of this channel may offer protection to neurons after several different types of injuries. Description (Set) Immune system abnormalities play key roles in development of nerve diseases such as multiple sclerosis. Pathologically activated immune cells initiate inflammatory cascades to cause neuronal damage. Specifically, T-cells induce cell death by delivering toxins to target cells. Granzyme B (GrB) is a well characterized T-cell granule toxin and is an important factor in mediating T-cell cytotoxicity. JHU scientists have determined that a potassium channel known as Kv1.3 is a key channel for GrB to enter cells. JHU scientists have determined that specific potassium channel blocker compounds, including siRNA sequences can protect neurons from GrB-induced toxicity.• Specific potassium channel inhibitors protect neurons from GrB-induced toxicity to reduce loss of viable neurons and lessen neurological symptoms of disease without affecting normal function of neurons.
• Kv1.3 channel blockers are advantageous because they do not cause the toxicity associated with non-specific ion channel inhibitors and could be used for a neuronal therapy with fewer side effects.
• Inhibitors target Kv1.3 channels to stimulate growth and proliferation of neuronal processes to increase nerve and muscle function.
• Administration of an Kv1.3 channel siRNA sequence modulates channel protein expression to reduce the effect of GrB on neuronal cells and maintain more optimal patient motor function.
• Specific Kv1.3 channel inhibitors stimulate proliferation of neuronal precursor cells which may form new neuronal connection and improve patient quality of life. Proposed Use (Set) This technology may be useful in drug development for most neurological diseases where injury to neurons may occur. This technology can be commercialized as therapeutic and prophylactic agents that block potassium channel activity. Therapeutic inhibitors can include compounds, antibodies and DNA/RNA molecules. This technology can also be commercialized as screening methods for blocking agents and therapeutic neurological methods.
Inventor(s): Nath, Avindra
Type of Offer: Licensing
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